Analysis of Optimal Treatment Sequencing of Surufatinib and Somatostatin Analogs in Neuroendocrine Tumors: A Retrospective Cohort Study

This is a multicenter retrospective cohort study designed to compare the efficacy differences between two treatment sequence-"first-line surufatinib and second-line somatostatin analogs (SSA)" versus "first-line SSA and second-line surufatinib"-in patients with advanced neuroendocrine tumors (NETs). The primary endpoint is progression-free survival (PFS) from the initiation of first-line therapy to progression on second-line treatment. Secondary endpoints include PFS for each individual line of therapy, safety profiles, and exploration of influencing factors. This study aims to identify the optimal treatment sequence and to provide real-world evidence for optimizing individualized treatment strategies for patients with advanced NETs, thereby informing clinical decision-making in routine practice.

Study Overview

• Status: Active, not recruiting
• Conditions: Neuroendocrine Tumors
• Intervention / Treatment: Drug: surufatinib; Drug: Somatostatin Analogs

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with histopathologically confirmed advanced G1/G2, SSTR2-positive NETs who received either first-line surufatinib followed by second-line SSA (Cohort A) or first-line SSA followed by second-line surufatinib (Cohort B). Patients with incomplete data for PFS assessment or who received combined systemic therapy during first-line or second-line treatment are excluded. Approximately 500 patients will be enrolled from six tertiary hospitals in China.

Description

Inclusion Criteria:

• Histopathologically confirmed locally advanced unresectable, metastatic, or postoperative recurrent neuroendocrine tumors (NETs), any primary site.
• Grade G1 or G2 based on Ki-67 index and/or mitotic count.
• Somatostatin receptor 2 (SSTR2) positive confirmed by immunohistochemistry (IHC) or somatostatin receptor imaging (e.g., 68Ga-PET/CT).
• Received one of the following two sequential treatment patterns:

Cohort A (Surufatinib → SSA): First-line surufatinib monotherapy followed by second-line long-acting somatostatin analog (SSA; lanreotide or octreotide long-acting release formulation) after disease progression.

Cohort B (SSA → Surufatinib): First-line long-acting SSA monotherapy followed by second-line surufatinib after disease progression.

• Each line of treatment duration at least 1 cycle (surufatinib ≥4 weeks; SSA ≥1 injection).
• Complete baseline clinical data, treatment start/end dates, and serial imaging evaluation reports available to determine progression-free survival for each line.
• Age ≥18 years at first-line treatment initiation.
• Permitted concomitant treatments during study drug administration (not considered as exclusion criteria):

Best supportive care (e.g., antidiarrheals, analgesics, hepatoprotective agents, symptomatic treatment for hormone secretion).

Local palliative interventions for focal lesions (e.g., transarterial embolization/chemoembolization, ablation for liver metastases) or cytoreductive surgery, provided they do not interrupt systemic study treatment or violate protocol.

For functional NETs, short-acting somatostatin analogs as rescue therapy for symptom control (frequency and dose to be recorded).

Exclusion Criteria:

• Received any combined systemic therapy (e.g., chemotherapy, other targeted therapy, immunotherapy) in addition to surufatinib or SSA during first-line or second-line treatment.
• Missing key baseline data (e.g., pathological grade, primary tumor site) or incomplete treatment/follow-up imaging data precluding accurate assessment of progression-free survival.
• Presence of active, uncontrolled serious infection or another active malignancy at the start of first-line treatment that may interfere with assessment of neuroendocrine tumor progression or patient survival prognosis (except cured skin basal cell carcinoma or carcinoma in situ).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort A (Surufatinib→SSA)	Drug: surufatinib; Oral tyrosine kinase inhibitor, 250mg or 300mg daily until disease progression or unacceptable toxicity.; Drug: Somatostatin Analogs; Long-acting release formulation of octreotide or lanreotide, administered via intramuscular or deep subcutaneous injection every 4 weeks until disease progression.
Cohort B (SSA→Surufatinib)	Drug: surufatinib; Oral tyrosine kinase inhibitor, 250mg or 300mg daily until disease progression or unacceptable toxicity.; Drug: Somatostatin Analogs; Long-acting release formulation of octreotide or lanreotide, administered via intramuscular or deep subcutaneous injection every 4 weeks until disease progression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PFS	From start of first-line treatment (either surufatinib or SSA) to disease progression on second-line treatment, assessed up to 60 months.

Collaborators and Investigators

• Sponsor: West China Hospital
• Collaborators: Beijing 302 Hospital; First Affiliated Hospital Xi'an Jiaotong University; The First Affiliated Hospital of Zhengzhou University; China-Japan Friendship Hospital; National Cancer Center/National Cancer Clinical Medical Research Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2026
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: April 8, 2026
• First Submitted That Met QC Criteria: April 9, 2026
• First Posted (Actual): April 16, 2026

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; surufatinib
• Other Study ID Numbers: 2026(562)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No